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Biomedical subjects

A Antonini

Publications and source records attributed to A Antonini.

At least 91 records · Page 5Linked to original sources
PubMed1995

Positron emission tomography in drug evaluation: influence of three different catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[18F]fluoro-L-dopa in rhesus monkey.

We compared the influence of three different catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier-added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) in one Rhesus monkey. All three COMT inhibitors improved 6-FDOPA availability in plasma, increased the specific uptake in the brain and thus improved 6-FDOPA uptake measurements using positron emission tomography (PET). Best results were obtained with Ro 40-7592.

Amidines↗
PubMed1994

Ultrastructural evidence for synaptic interactions between thalamocortical axons and subplate neurons.

Thalamic axons are known to accumulate in the subplate for a protracted period prior to invading the cortical plate and contacting their ultimate targets, the neurons of layer 4. We have examined the synaptic contacts made by visual and somatosensory thalamic axons during the transition period in which axons begin to leave the subplate and invade the cortical plate in the ferret. We first determined when geniculocortical axons leave the subplate and begin to grow into layer 4 of the visual cortex by injecting 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine (Dil) into the lateral geniculate nucleus (LGN). By birth most LGN axons are still confined to the subplate. Over the next 10 days LGN axons grow into layer 4, but many axons retain axonal branches within the subplate. To establish whether thalamic axons make synaptic contacts within the subplate, the anterograde tracer PHA-L was injected into thalamic nuclei of neonatal ferrets between postnatal day 3 and 12 to label thalamic axons at the electron microscope level. The analysis of the PHA-L injections confirmed the Dil data regarding the timing of ingrowth of thalamic axons into the cortical plate. At the electron microscope level, PHA-L-labelled axons were found to form synaptic contacts in the subplate. The thalamic axon terminals were presynaptic primarily to dendritic shafts and dendritic spines. Between postnatal days 12 and 20 labelled synapses were also observed within layer 4 of the cortex. The ultrastructural appearance of the synapses did not differ significantly in the subplate and cortical plate, with regard to type of postsynaptic profiles, length of postsynaptic density or presynaptic terminal size. These observations provide direct evidence that thalamocortical axons make synaptic contacts with subplate neurons, the only cell type within the subplate possessing mature dendrites and dendritic spines; they also suggest that functional interactions between thalamic axons and subplate neurons could play a role in the establishment of appropriate thalamocortical connections.

Animals↗
PubMed1994

Side effects of the catechol-O-methyl-transferase inhibitor Ro 40-7592 in rabbits.

Catechol-O-methyl-transferase inhibitors are promising drugs in Parkinson's disease since these drugs enhance levodopa effects and increase their duration. However, since these compounds block a pathway for the peripheral metabolism of catecholamines, they may also produce side effects related to elevation of catecholamines in plasma. We investigated the adverse effects of Ro 40-7592 in rabbits and the relationship of Ro 40-7592 to norepinephrine plasma levels. Intravenous administration of Ro 40-7592 in rabbits induced elevation of norepinephrine plasma levels in old animals after bolus injection of a dose three times the highest dose actually recommended to be taken orally by humans. Though Ro 40-7592 appears safe for humans, special precautions may be needed in patients with a high risk of adrenergic hyperactivity.

Animals↗
PubMed1994

Comparison of 123I-IBZM SPECT and 11C-raclopride PET findings in patients with parkinsonism.

We compared the results of 123I-iodobenzamide (123I-IBZM) single photon emission computed tomography (SPECT) and 11C-raclopride positron emission tomography (PET) in 22 patients with parkinsonism. Nineteen patients were clinically diagnosed as having Parkinson's disease, two patients presented with atypical parkinsonism (i.e. clinical signs of Parkinson's disease and a subsequent poor response to dopamimetic drugs) and one patient was diagnosed as having Wilson's disease. All patients were drug naive. The SPECT data were semiquantitatively evaluated by calculating the ratios of striatal (basal ganglia, BG) IBZM binding to IBZM binding in various reference areas, i.e. the frontal cortex (BG/FC), the occipital cortex (BG/OC) and the cerebellum (BG/CE). In PET studies similar regions of interest were derived and ratios of striatal to cerebellar raclopride activity were determined. 123I-IBZM SPECT results significantly correlated to specific 11C-raclopride binding. This correlation was not significantly different when the frontal cortex (P = 0.05, r = 0.42), occipital cortex (P < 0.05), r = 0.44) or cerebellum (P 0.05, r = 0.45) were used as reference regions for non-specific IBZM binding. In comparison to PET ratios the SPECT BG/CE showed a higher variance (S.E.M. = 0.1) than BG/FC (S.E.M. = 0.05) and BG/OC (S.E.M. = 0.06) ratios. Thus, for the calculation of specific striatal IBZM binding one would prefer the frontal or occipital cortex as reference. However, when only those 19 patients with a clinical diagnosis of Parkinson's disease and increased specific 11C-raclopride binding were considered, no significant correlation was obtained. Qualitative changes of dopamine D2 receptor binding, such as asymmetry, were equally recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride.

We investigated in vivo D2 receptor binding using 11C-raclopride and PET in the striatum of 17 subjects with the narcoleptic syndrome. Putamen and caudate nucleus 11C-raclopride uptake was comparable in the total patient group and controls, and the tracer uptake was similar in the HLA-DR2-positive (n = 12) and HLA-DR2-negative (n = 5) narcoleptic subjects. There was a significant increase in 11C-raclopride uptake in the putamen of narcoleptic subjects older than 31 years (n = 11) when compared with age-matched controls (n = 15). There was no evidence of involvement of the striatal D2 dopaminergic neurotransmitter system in the basic pathophysiology of the narcoleptic syndrome despite an age-related increase in putaminal 11C-raclopride uptake.

Adolescent↗
PubMed1994

Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy.

We have studied 25 patients with interictal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after selective surgery for temporal lobe epilepsy (TLE). Based on the findings of the presurgical evaluation, including ictal intracranial EEGs, histopathologic findings, and the postoperative outcome, we classified the patients in three subgroups: (1) patients with TLE of lateral temporal origin (n = 5), (2) patients with mesiobasal limbic TLE associated with mesial gliosis (n = 14), and (3) patients with mesiobasal limbic TLE and small mesial tumors (n = 6). Postoperatively, patients with mesiobasal limbic TLE and mesial gliosis and five of six patients with mesiobasal limbic TLE and mesial tumors were seizure-free; the remaining sixth patient had one generalized seizure. Patients with TLE of lateral temporal origin had more than 90% reduction of seizure frequency. The main postoperative metabolic findings were as follows: (1) marked increase of regional cerebral metabolic rate of glucose (rCMRglu), both in the ipsilateral and, significantly, in the contralateral hemisphere in patients with mesiobasal limbic TLE and mesial gliosis-the changes of brain metabolism were characteristic for patients with the syndrome of "mesial temporal lobe epilepsy" (MTLE); (2) decrease of rCMRglu values in the contralateral mesiobasal temporal lobe (TL) cortex in all patient groups--the reduction of rCMRglu in homologous brain structures contralateral to the operated side provides evidence for stronger interhemispheric connections between both mesial TL structures than were hitherto supposed; and (3) a trend toward a normalization of rCMRglu values in the ipsilateral temporal neocortex 12 months after surgery in patients with MTLE syndrome.

Adolescent↗
PubMed1994

Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease.

We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C-raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons.

Adolescent↗
PubMed1994

[11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors.

We studied cerebral dopamine D2-receptor binding using [11C]raclopride and PET in 18 previously untreated patients with Parkinson's disease (PD) and 14 healthy volunteer subjects. Sixteen patients were scanned before and after 3 to 4 months of stable oral therapy with either L-dopa (300 mg/d) (n = 7) or lisuride (0.8 to 1.2 mg/d) (n = 9). Two additional patients were investigated before and after a continuous IV infusion of L-dopa. In addition, we studied the effect of acute IV L-dopa and lisuride administration on [11C]raclopride binding in a healthy rhesus monkey. At baseline, PD patients showed higher uptake values in the putamen than did healthy subjects (p < 0.0001). Oral lisuride treatment lowered [11C]raclopride uptake in the putamen (-19%) and in the caudate nucleus (-15%) compared with baseline, but the difference did not reach significance upon Bonferroni correction for multiple comparisons. However, putamen tracer uptake returned to baseline in two patients when we repeated [11C]raclopride scans 4 days after lisuride withdrawal. Oral L-dopa treatment did not induce changes in the putamen or caudate nucleus indices. Acute lisuride (25 micrograms) administration in a healthy monkey reduced striatal uptake values, but acute injection of L-dopa (300 mg) did not. The results suggest that lisuride blocks [11C]raclopride binding at dopamine D2-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D2-receptor density in PD patients.

Adult↗
PubMed1994

Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol.

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood.

Animals↗
PubMed1993

Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [11C]-raclopride.

Human post-mortem and animal experimental results suggest a decline of the cerebral dopaminergic neuronal system with age. In this study, the radiotracer [11C]raclopride (dopamine D2 antagonist) and positron emission tomography were applied to determine the effect of age on striatal dopamine D2 receptors in 32 healthy volunteer subjects (age range 21-68 years). Subjects were divided in two age groups on the basis of median age (31 years). An index for specific tracer uptake was calculated for caudate nucleus and putamen. Uptake indices in the older group of subjects were reduced on average 26% in putamen and 20% in caudate nucleus. The decline appeared to be steep until 30 years, but slower afterwards. After 30 years of age the decline of specific raclopride binding was found to be 0.6% per year. These results suggest that dopamine D2 receptor binding sites (mainly post-synaptically located) decrease as a consequence of normal aging in parallel with the decline of the pre-synaptic nigrostriatal dopaminergic system.

Adult↗
PubMed1993

Rapid remodeling of axonal arbors in the visual cortex.

If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity.

Animals↗
PubMed1993

Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride.

Human postmortem and animal experimental results suggest a decline of the cerebral dopaminergic neuronal system with age. In this study, the radiotracer carbon 11-labeled-raclopride and positron emission tomography were applied to determine the effect of age on striatal D2 dopamine receptors in 32 healthy volunteer subjects (age range, 21 to 68 years; median, 31 years). An index of specific 11C-raclopride binding was calculated for putamen, caudate nucleus, and other brain regions in each subject. A significant decrease with age of the index for specific tracer uptake was found in putamen and caudate nucleus. The decrease was steep until 30 years, but slower afterward. After approximately 30 years of age, the decline of specific 11C-raclopride binding in putamen was found to be 0.6% per year. Our results suggest that D2 dopamine receptor binding sites (mainly postsynaptically located) decrease as a consequence of normal aging in parallel with the decline of the presynaptic nigrostriatal dopaminergic neuronal system.

Adult↗
PubMed1993

Increased striatal glucose consumption in Sydenham's chorea.

Positron emission tomography and 18F-fluorodeoxyglucose were used to measure the regional cerebral glucose consumption in a 15-year-old choreatic girl with classical Sydenham's chorea shortly after the onset of hyperkinetic movements and 5 months later after chorea had resolved and in a 74-year-old hemichoreatic woman with long-standing hyperkinesia as a residuum of Sydenham's chorea in adolescence. Whereas cerebellar, thalamic, and cortical glucose consumption was within normal limits in both patients, lentiform and caudate glucose consumption was significantly increased in both hemispheres of the 15-year-old patient and in the hemisphere contralateral to the chorea in the 74-year-old patient. In the younger patient, striatal glucose consumption returned to normal after her hyperkinesia had disappeared with antibiotic therapy. The observation of an increase in striatal glucose consumption in Sydenham's chorea, in contrast to the decrease of this variable encountered in the vast majority of other choreatic disorders, leads to questioning the pathophysiology of chorea in humans and suggests the use of emission tomographic measurement of variables related to cerebral energy metabolism for differential diagnosis in choreatic disorders.

Adolescent↗
PubMed1993

Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET).

The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50-60% after 24-36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3-7 h after administration and amounted to 40 to 75% at the peak time (20-29 h). This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.

Adult↗
PubMed1993

Mesiobasal versus lateral temporal lobe epilepsy: metabolic differences in the temporal lobe shown by interictal 18F-FDG positron emission tomography.

Metabolic abnormalities in the temporal lobe (TL) of 25 patients suffering from temporal lobe epilepsy of mesiobasal or lateral TL origin have been investigated using interictal [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). The epileptogenic area was determined by ictal EEG recordings using foramen ovale and scalp electrodes in 20 patients, and by the use of stereo-electroencephalography in one patient. Four patients with structural lesions on their MRIs had noninvasive ictal surface EEG recordings. Sixteen patients had a clear-cut mesiobasal seizure onset, and in five patients the seizures originated from the lateral temporal neocortex. Twenty-four patients underwent selective surgery. Patients with temporal limbic seizures associated with mesial gliosis (n = 15) had the lowest FDG uptake in the entire TL, followed by patients with lateral temporal seizure origin (n = 5). Patients with tumors located in the mesiobasal TL (n = 5) showed, in general, only a slight decrease of glucose metabolism in all TL structures. There was no clear-cut correlation between the degree of hypometabolism and the location of EEG-defined epileptogenic focus. The metabolic pattern, however, differed between the patient groups and allowed a discrimination between patients of mesial temporal and lateral temporal seizure onset.

Adolescent↗
PubMed1993

T2 relaxation time in patients with Parkinson's disease.

Postmortem studies of patients with Parkinson's disease (PD) reveal an increase in iron concentration in the substantia nigra. Iron content in the brain is associated with decreased signal intensity on T2-weighted MRI. We measured in vivo the T2 relaxation time in 30 PD patients and 33 healthy volunteer subjects, using a 1.5-T whole-body MRI system. In comparison with healthy controls, T2 values in PD patients were reduced in the following brain regions: substantia nigra, caudate nucleus, and putamen. Due to the overlap between patients and control subjects, we could not differentiate, in a given patient, healthy from diseased state on the basis of T2 relaxation time. Our findings support the notion of increased iron deposition in the substantia nigra of patients with PD. However, the shortening of T2 values in the substantia nigra did not correlate with disease duration nor with clinical severity.

Adult↗
PubMed1993

Development of individual geniculocortical arbors in cat striate cortex and effects of binocular impulse blockade.

This study analyzes the morphological changes in geniculocortical axons terminating in the primary visual cortex of the cat, during the period in which, in normal development, the terminals in layer IV undergo an eye-specific segregation. Geniculocortical afferent fibers were filled anterogradely by the Phaseolus lectin (PHA-L) injected into the main laminae of the LGN. After standard immunohistochemical procedures, single axons were serially reconstructed in two or three dimensions. Experiments were performed in normal kittens and in kittens in which retinal activity was continuously blocked by repeated intraocular injections of TTX. In normal kittens, arbors were reconstructed at four different ages (19, 23, 30-31, and 39 days postnatally) spanning the period during which the geniculocortical projection segregates into eye-specific columns in layer IV (LeVay et al., 1978). Results reveal that sparse but widely extending branches characteristic of young arbors are eliminated during normal development at the same time as selected portions of the arbor grow considerably in length and complexity. The terminal arborizations also subdivide into distinct patches of terminals, consistent with the segregation of left and right eye afferents. In TTX-treated animals, axonal arbors reconstructed at postnatal days 23, 29, and 39 show a complexity and extent of terminal arborization similar to that of normal animals, though more variable in size and degree of elaboration. No progressive changes are evident with age. Further, the majority of arbors reconstructed from TTX-treated animals lack the patchy organization typical of normal animals.

Afferent Pathways↗